Agelastatin A is an oroidin alkaloid extracted from an axinellid sponge, Agelas dendromorpha. It has anti-neoplastic activities against multiple cancers including breast cancer, lung cancer, colon cancer, head and neck cancer, and bladder cancer (see, e.g., M. D'Ambrosio et al. J Chem Soc Chem Commun, 1993, 1305; M. D'Ambrosio et al. Helv. Chim. Acta, 1996, 79, 727-735; and M. D'Ambrosio et al. Helv. Chim. Acta, 1994, 79, 727-735). It has been shown to be 1.5 to 16 times more potent than Cisplatin (G. R. Pettit et al. Oncol Res, 2005, 15, 11-20). Recently it was shown that AA has anti-osteopontin (OPN) activity (K. Mason et al. Mol Cancer Ther, 2008, 7, 548-558).
OPN plays an important role in cancer biology and mediates cell proliferation, invasion, metastasis, and angiogenesis. High expression of OPN is found in primary brain tumors including primary CNS lymphoma (PCNSL) and glioblastoma multiforme (GBM). As such, OPN is a valid molecular target for therapeutic development for these aggressive brain tumors.
Current treatments for brain tumors such as PCNSL, GBM, and metastatic breast cancer of the brain are not very effective and carry significant toxicities. Therapeutic agents with better efficacy and toxicity profile are urgently needed.